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Article

Biological Impact of Target Fragments on Proton Treatment Plans: An Analysis Based on the Current Cross-Section Data and a Full Mixed Field Approach

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Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics, (INFN), 38123 Trento, Italy
2
Department of Physics, University of Trento, 38123 Trento, Italy
3
The Department of Radiation Research and Proton Radiotherapy, Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland
4
“Roma Tre” Section, INFN—National Institute for Nuclear Physics, 00146 Roma, Italy
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Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, 64291 Darmstadt, Germany
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“Pavia” Section, INFN—National Institute for Nuclear Physics, 6-27100 Pavia, Italy
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Laboratori Nazionali del Sud, INFN—National Institute for Nuclear Physics, 95125 Catania, Italy
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Institut für Physik Kondensierter Materie, Technische Universität, 64289 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Currently with: Department of Physics, University of Padova, 35131 Padova, Italy.
Currently with: ELI-Beamlines, Institute of Physics (FZU), Czech Academy of Sciences, 18200 Prague, Czech Republic.
Academic Editors: Dimitris Emfietzoglou and Sebastien Incerti
Cancers 2021, 13(19), 4768; https://doi.org/10.3390/cancers13194768
Received: 23 July 2021 / Revised: 13 September 2021 / Accepted: 13 September 2021 / Published: 24 September 2021
Proton therapy is now an established external radiotherapy modality for cancer treatment. Clinical routine currently neglects the radiobiological impact of nuclear target fragments even if experimental evidences show a significant enhancement in cell-killing effect due to secondary particles. This paper quantifies the contribution of proton target fragments of different charge in different irradiation scenarios and compares the computationally predicted corrections to the overall biological dose with experimental data.
Clinical routine in proton therapy currently neglects the radiobiological impact of nuclear target fragments generated by proton beams. This is partially due to the difficult characterization of the irradiation field. The detection of low energetic fragments, secondary protons and fragments, is in fact challenging due to their very short range. However, considering their low residual energy and therefore high LET, the possible contribution of such heavy particles to the overall biological effect could be not negligible. In this context, we performed a systematic analysis aimed at an explicit assessment of the RBE (relative biological effectiveness, i.e., the ratio of photon to proton physical dose needed to achieve the same biological effect) contribution of target fragments in the biological dose calculations of proton fields. The TOPAS Monte Carlo code has been used to characterize the radiation field, i.e., for the scoring of primary protons and fragments in an exemplary water target. TRiP98, in combination with LEM IV RBE tables, was then employed to evaluate the RBE with a mixed field approach accounting for fragments’ contributions. The results were compared with that obtained by considering only primary protons for the pristine beam and spread out Bragg peak (SOBP) irradiations, in order to estimate the relative weight of target fragments to the overall RBE. A sensitivity analysis of the secondary particles production cross-sections to the biological dose has been also carried out in this study. Finally, our modeling approach was applied to the analysis of a selection of cell survival and RBE data extracted from published in vitro studies. Our results indicate that, for high energy proton beams, the main contribution to the biological effect due to the secondary particles can be attributed to secondary protons, while the contribution of heavier fragments is mainly due to helium. The impact of target fragments on the biological dose is maximized in the entrance channels and for small α/β values. When applied to the description of survival data, model predictions including all fragments allowed better agreement to experimental data at high energies, while a minor effect was observed in the peak region. An improved description was also obtained when including the fragments’ contribution to describe RBE data. Overall, this analysis indicates that a minor contribution can be expected to the overall RBE resulting from target fragments. However, considering the fragmentation effects can improve the agreement with experimental data for high energy proton beams. View Full-Text
Keywords: proton therapy; relative biological effectiveness (RBE); mixed field model; Monte Carlo; TOPAS; biophysical dose-response models proton therapy; relative biological effectiveness (RBE); mixed field model; Monte Carlo; TOPAS; biophysical dose-response models
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MDPI and ACS Style

Bellinzona, E.V.; Grzanka, L.; Attili, A.; Tommasino, F.; Friedrich, T.; Krämer, M.; Scholz, M.; Battistoni, G.; Embriaco, A.; Chiappara, D.; Cirrone, G.A.P.; Petringa, G.; Durante, M.; Scifoni, E. Biological Impact of Target Fragments on Proton Treatment Plans: An Analysis Based on the Current Cross-Section Data and a Full Mixed Field Approach. Cancers 2021, 13, 4768. https://doi.org/10.3390/cancers13194768

AMA Style

Bellinzona EV, Grzanka L, Attili A, Tommasino F, Friedrich T, Krämer M, Scholz M, Battistoni G, Embriaco A, Chiappara D, Cirrone GAP, Petringa G, Durante M, Scifoni E. Biological Impact of Target Fragments on Proton Treatment Plans: An Analysis Based on the Current Cross-Section Data and a Full Mixed Field Approach. Cancers. 2021; 13(19):4768. https://doi.org/10.3390/cancers13194768

Chicago/Turabian Style

Bellinzona, Elettra V., Leszek Grzanka, Andrea Attili, Francesco Tommasino, Thomas Friedrich, Michael Krämer, Michael Scholz, Giuseppe Battistoni, Alessia Embriaco, Davide Chiappara, Giuseppe A.P. Cirrone, Giada Petringa, Marco Durante, and Emanuele Scifoni. 2021. "Biological Impact of Target Fragments on Proton Treatment Plans: An Analysis Based on the Current Cross-Section Data and a Full Mixed Field Approach" Cancers 13, no. 19: 4768. https://doi.org/10.3390/cancers13194768

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